Analysis of the free amino acids of Fasciola hepatica extracted from the worm reveals that between 25-35% of the total is proline. Analysis of the free amino acids in the bile fluid of rats infected with Fasciola hepatica shows a very marked increase in the level of proline, beginning with about a 100 fold rise 25 days after infection and increasing to about 3000-5000 times after the worms enter the ducts which occurs about the 70th day. There is also an increase in the concentrations of the other free amino acids. However, the increase in any of these amino acids is less than 10 fold and is detectable only after the worms have entered the bile duct, while proline increases over 100 fold 6 to 7 weeks before the worms enter the bile ducts. At the time this increase is detected there is a concomitant increase in the bile duct endothelium of the host resulting in a thickened, extensively folded, endothelium and a dilated duct, in preparation, as it were, for the living site of Fasciola hepatica. From studies on the enzymatic apparatus of the worm it has been concluded that the worm is the source of the proline. Current studies indicate that proline from Fasciola is responsible for the hyperplasia of the bile duct and that infusion of proline into healthy rats can cause such hyperplasia. How proline mediates this effect in the disease will be determined. The cellular basis for the proline effect and its possible relationship to collagen synthesis will also be explored. Another area to be examined is the effect of proline on the other amino acids in bile and on the dynamics of amino acid interactions in various host tissues. Furthermore, a similar type of proline production occurs in the human blood fluke Schistosoma mansoni and the human liver fluke Clonorchis. Studies proposed here would determine the prescursors, enzyme characteristics and control mechanisms of proline biosynthesis in these trematodes and the significance to pathology of diseases caused by these flukes.